Possible role for gap-junctional remodeling
in ischemic ST depression on the ECG
In The 33rd International Congress on Electrocardiology,
Cologne, June 2006.
A more comprehensive version of this paper was published in Heart Rhythm, 2007. In this more recent paper we discuss also the role of geometric factors: more extensive ischemic zones make overlying ST depression more likely. The limiting case is global subendocardial ischemia. As we have shown at the ICE 2007 conference, this would lead to a typical "stress-test ECG".
question Experiments using coronary artery occlusion to produce partial-thickness ischemia in dogs have shown both ST-segment depression and elevation in overlying epicardial leads. Recent computer simulations with realistic anisotropic models predict local epicardial ST elevation and remote depression . Changes in tissue conductivity modify the ST deviation pattern . Reperfusion after ischemia is followed by a redistribution of connexins towards the lateral sides of the myocytes. It is not known if the "lateralized" connexins form gap junctions. If they do, anisotropy of intracellular conductivity would be reduced. We hypothesized that this change of conductivity would account for local epicardial ST depression during a subsequent ischemia.
methods A computer model of the human heart and torso was used to compute differences be tween ST and TQ segment potentials on the epicardial and thoracic surfaces. The model included a realistic cardiac anatomy, anisotropic ventricles with transmural fiber rotation, ventricular blood, and thoracic inhomogeneities. ST deviation patterns were computed for normal and reduced intracellular anisotropy ratio, the latter representing gap-junctional remodeling.
results The assumedly normal conductivity values lead to ST elevation on the epicardium and in surface leads overlying the ischemia. However, a reduced intracellular anisotropy would lead to ST depression in the same region.
conclusion Connexins are lateralized following reperfusion. Our results show that, if lateralized connexins form sufficient gap junctions, this would influence ST deviation during a subsequent ischemia. This effect could account for local epicardial ST depression. Direct measurements of the changes in anisotropic bidomain conductivities are needed to validate this hypothesis.
 B. Hopenfeld et al. J. Cardiovasc. Electrophysiol. 15:1200, 2004.
This work was supported by the Natural Sciences and Engineering Research Council of Canada. The work of M. Potse was supported in part by FRSQ, Québec, and in part by The Netherlands Organization for Scientific Research (NWO). Computational resources for this work were provided by the Réseau québécois de calcul de haute performance (RQCHP).
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